Methods and Devices for Determining Sensing Device Usability

ABSTRACT

Methods and devices for determining device usability, e.g., for point of care assay devices. In one embodiment, the invention is to a method of determining device usability in a sensing device, including the steps of: providing a device comprising a first electrical pad; a second electrical pad; and a first polymer layer contacting at least a portion of the first and the second electrical pads and a second polymer layer contacting the first polymer layer and not the first and second electrical pads; applying a potential across the first and the second electrical pads; measuring an electrical property associated with the first and the second polymer layers; and determining whether the measured electrical property associated with the first and the second polymer layers has exceeded a threshold level associated with the device usability.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.61/540,026 filed Sep. 28, 2011 and to U.S. Provisional Application No.61/503,234 filed Jun. 30, 2011, the entireties of which are incorporatedherein by reference.

FIELD OF THE INVENTION

The present invention relates to methods and devices for determiningsensing device usability. In particular, the methods and devices can beused for determining device usability through application of a potentialacross two electrical pads and two or more polymer layers there betweenand measuring an electrical property of the polymer layers to determinewhether a device has exceeded a threshold level associated with deviceusability.

BACKGROUND OF THE INVENTION

A multitude of laboratory tests for analytes of interest are performedon biological samples for diagnosis, screening, disease staging,forensic analysis, pregnancy testing and drug testing, among others.While a few qualitative tests, such as glucose, prothrombin, andpregnancy tests, have been reduced to simple kits for a patient's homeuse, the majority of quantitative tests still require the expertise oftrained technicians in a laboratory setting using sophisticatedinstruments. Laboratory testing increases the cost of analysis anddelays the patient's or clinician's receipt of the results. In manycircumstances, this delay can be detrimental to the patient's conditionor prognosis, such as for example the analysis of markers indicatingmyocardial infarction and heart failure. In these and similar criticalsituations, it is advantageous to perform such analyses at thepoint-of-care, accurately, inexpensively and with minimal delay.

Point-of-care sample analysis systems are generally based on a reusablereading apparatus that performs sample tests using a disposable device(e.g., a cartridge or strip) that contains analytical elements (e.g.,electrodes or optics for sensing analytes such as, for example, pH,oxygen, or glucose). The disposable device can optionally includefluidic elements (e.g., conduits for receiving and delivering the sampleto the electrodes or optics), calibrant elements (e.g., fluids forstandardizing the electrodes with a known concentration of the analyte),and dyes with known extinction coefficients for standardizing optics.

Point-of-care sample testing systems eliminate the time-consuming needto send a sample to a central laboratory for testing. Point-of-caresample testing systems allow a user e.g. a nurse and physician, at thebedside of a patient, to obtain reliable, quantitative, analyticalresults, comparable in quality to that which would be obtained in alaboratory. In operation, the user may select a device with the requiredpanel of tests (e.g., electrolytes, metabolites, cardiac markers and thelike), draw a sample, dispense it into the device, optionally seal thedevice, and insert the device into the reading apparatus to communicatethe data to an LIS/HIS for analysis. An example of such a system is thei-STAT® system sold by Abbott Point-of-Care, Inc., Princeton, N.J., USA.The i-STAT® portable blood analysis system typically comprisesWi-Fi-enabled reader instruments that work in conjunction withsingle-use blood testing cartridges that contain sensors for variousanalytes. For further information on the i-STAT® portable blood analysissystem, see http://www.abbottpointofcare.com/.

Analyzers, such as a self-contained disposable sensing device orcartridge and a reader or instrument, are further described in nowexpired U.S. Pat. No. 5,096,669 to Lauks, et al., the entirety of whichis incorporated herein by reference. In operation, a fluid sample to bemeasured is drawn into a device and the device is inserted into thereader through a slotted opening. Data generated from measurementsperformed by the reader may be output to a display and/or other outputdevice, such as a printer, or, as described in greater detail below, viaa wireless network connection. The disposable device may contain sensingarrays and several cavities and conduits that perform sample collection,provide reagents for use in measurement and sensor calibration, andtransport fluids to and from the sensors. Optionally, reagents may bemixed into the sample for testing. Sensing arrays in the device measurethe specific chemical species in the fluid sample being tested. Theelectrochemical sensors are exposed to and react with the fluid sampleto be measured generating electrical currents and potentials indicativeof the measurements being performed. The electrochemical sensors may beconstructed dry and when the calibrant fluid flows over theelectrochemical sensors, the sensors easily “wet up” and are operationaland stable for calibration and composition measurements. Thesecharacteristics provide many packaging and storage advantages, includinga long shelf life. Each of the sensing arrays may comprise an array ofconventional electrical contacts, an array of electrochemical sensors,and circuitry for connecting individual sensors to individual contacts.The electrical signals are communicated to a reader enabled to performcalculations and to display data, such as the concentration of theresults of the measurement.

Although the particular order in which the sampling and analytical stepsoccur may vary between different point-of-care systems and providers,the objective of providing rapid sample test results in close proximityto a patient remains. The reading apparatus (e.g., i-STAT® or otherwireless analyzer) may then perform a test cycle (i.e., all the otheranalytical steps required to perform the tests). Such simplicity givesthe physician quicker insight into a patient's physiological status and,by reducing the time for diagnosis, enables a quicker decision by thephysician on the appropriate treatment, thus enhancing the likelihood ofa successful patient treatment.

In the emergency room and other acute-care locations within a hospital,the types of sample tests required for individual patients can varywidely. Thus, point-of-care systems generally offer a range ofdisposable devices configured to perform different sample tests, orcombinations of such tests. For example, for blood analysis devices, inaddition to traditional blood tests, including oxygen, carbon dioxide,pH, potassium, sodium, magnesium, calcium, chloride, phosphate,hematocrit, glucose, urea (e.g., BUN), creatinine and liver enzymes,other tests may include, for example, prothrombin time (PT), activatedclotting time (ACT), activated partial thromboplastin time (APTT),troponin, creatine kinase MB (CKMB), and lactate. Although devicestypically contain between one and ten tests, it will be appreciated bypersons of ordinary skill in the art that any number of tests may becontained in a device.

A given hospital may use numerous different types of test devices andtest instruments at multiple point-of-care testing locations within thehospital. These locations can include, for example, an emergency room(ER), a critical care unit (CCU), a pediatric intensive care unit(PICU), an intensive care unit (ICU), a renal dialysis unit (RDU), anoperating room (OR), a cardiovascular operating room (CVOR), generalwards (GW), and the like. Other non-hospital-based locations wheremedical care is delivered, include, for example, MASH units, nursinghomes, and cruise, commercial, and military ships.

In some cases, cartridges have a shelf life, which may vary widelydepending on the specific cartridge as well as upon storage conditions.For example, some cartridges may have a shelf life of about six to aboutnine months when refrigerated, but a much more limited shelf life, e.g.,about two weeks at room temperature, or, more specifically, about tenweeks at up to about 30° C. As a result, hospitals typically storecartridges at a central refrigerated location, and deliver cartridges tospecific locations, as demand requires. These locations can include, forexample, an emergency room (ER), critical care unit (CCU), pediatricintensive care unit (PICU), intensive care unit (ICU), renal dialysisunit (RDU), operating room (OR), cardiovascular operating room (CVOR)and general wards (GW). These locations may or may not have availablerefrigerated storage, and this will influence product lifetime and, as aresult, the inventory they will hold. Further complicating devicemanagement is the fact that a given user, such as a hospital, may usemultiple types of cartridges, each having a different shelf life.Alternatively, the user may be a physician's office laboratory orvisiting nurse service. However, the need to ensure quality remains thesame.

U.S. Patent Appl. No. U.S. 2009/0119047 to Zelin et al., the entirety ofwhich is incorporated herein by reference, discloses an improved qualityassurance system and method for point-of-care testing. It providesquality assurance for laboratory quality tests performed by a bloodanalysis system at the point of patient care without the need forrunning liquid-based quality control materials on the analysis system.Quality assurance of a quantitative physiological sample test system isperformed without using a quality control sample by monitoring thethermal and temporal stress of a component used with the test system.Alert information is generated that indicates that the component hasfailed quality assurance when the thermal and temporal stress exceeds apredetermined thermal-temporal stress threshold.

U.S. Pat. No. 7,612,325 to Watkins Jr., et al., the entirety of which isincorporated herein by reference, discloses electrical sensor formonitoring degradation of products from environmental stressors anddescribes an environmental degradation sensor for environmentallysensitive products such as food, pharmaceuticals or cosmetic productsprovides the degraded state and estimated remaining life of the product.The sensor is made of a polymeric matrix and conductive filler. Acontrol agent, selected to adjust a reaction rate of the sensor toenvironmental conditions, allows correlation of an electrical propertyof the sensor to a degraded state of the product.

In general, the principles of operation for existing types oftime/temperature indicators can be categorized as physical, chemical andelectrical. Examples of physical and chemical methods include colorchange of polymeric materials, chemical reactions of two elements,physical masking of a marker, melting of a temperature sensitivematerial and the like.

However, the use of many existing indicators adds significant cost andcomplexity to the devices they are intended to monitor. This is aparticularly apparent issue for single-use blood testing cartridges andelectrochemical strip devices, e.g., glucose blood testing strips usedby diabetics. Consequently, the need remains for improved low costtime-temperature indicators that are amenable to direct integration intoa device manufacturing workflow. The need also exists for methods anddevices for correcting signals in such devices.

SUMMARY OF THE INVENTION

The present invention relates to sensing devices having first and secondelectrical pads and having a first polymer layer and a second polymerlayer disposed there between. Preferably, the first polymer layer has adifferent conductivity and impedance than the second polymer layer. Overtime and/or at elevated temperatures, the polymer layers may migrate ordiffuse into one another causing an increase in conductivity (andreduction in resistivity) between the two electrical pads. As a result,an electrical property associated with the first and second electricalpads may be correlated to device usability and/or may be used to derivea correction factor that may be applied to a device signal to determinea corrected device signal.

In one embodiment, for example, the invention is to a method ofdetermining device usability, comprising: providing a device comprisinga first electrical pad; a second electrical pad; and a first polymerlayer contacting at least a portion of the first and the secondelectrical pads, e.g., contact pads. The device also includes a secondpolymer layer contacting the first polymer layer and not the first andthe second electrical pads. The method includes applying a potentialacross the first and the second electrical pads; measuring an electricalproperty associated with the first and the second polymer layers; anddetermining whether the measured electrical property associated with thefirst and the second polymer layers has exceeded a threshold levelassociated with the device usability. The first polymer layer may be acontinuous polymer layer.

In another embodiment, the invention is to a device having a usabilitythreshold comprising a first electrical pad; a second electrical pad; afirst polymer layer electrically contacting at least a portion of thefirst and the second electrical pads; and a second polymer layercontacting the first polymer layer but not contacting the first and thesecond electrical pads. The first and the second polymer layers have anelectrical property associated with the device usability threshold.

In another embodiment, the invention is to a device comprising a sensor;a first polymer layer formed on a surface of the device; a secondpolymer layer in contact with the first polymer layer, e.g., formed onthe first polymer layer; a first electrical pad; and a second electricalpad. The surface comprises the first and the second electrical padspositioned adjacent to one another and a space there between. The firstpolymer layer covers at least a portion of the first and the secondelectrical pads and at least a portion of the space between the layers,and the second polymer layer contacts the first polymer layer but notthe first and the second electrical pads. In the device, a preselectedpotential or potential cycle is applied to the first and the secondelectrical pads and an impedance or current associated with the firstand the second polymer layers is measured. The measured impedance orcurrent is converted to a value indicative of an average shelf life timeremaining for other devices from a same manufacturing lot of the device.

In yet another embodiment, the invention is to a method of determiningdevice usability comprising providing a device comprising a firstelectrical pad; a second electrical pad; a first polymer layercontacting at least a portion of the first and the second electricalpads; and a second polymer layer contacting the first polymer layer butnot the first and the second electrical pads. A potential is appliedacross the first and the second electrical pads, and an electricalproperty associated with the first and the second polymer layers ismeasured. A correction factor associated with the measured electricalproperty is determined, which is applied to a signal generated by asensor to produce a corrected signal.

In preferred embodiments, the first polymer layer and/or the secondpolymer layer comprises a polymer matrix, a plasticizer and an organicsalt. For example, the first polymer layer and/or the second polymerlayer may comprise from 20 to 40 wt. % polymer matrix. The polymermatrix may comprise a polymer selected from the group consisting ofpolyvinyl chloride, polyurethane, polyvinylacetate, carboxylated PVC,hydroxylated PVC and polydimethyl siloxane. The first polymer layeroptionally comprises from 60 to 80% plasticizer, which may be selectedfrom the group consisting of trioctyl phosphate (TOP), nitrophenyloctylether (NPOE), bisethylhexylsebacate (BEHS), trimethyl trimellitate(TMTT), dioctyl adipate (DOA) and diisobutyl phthalate (DIBP). The firstpolymer layer and/or the second polymer layer may comprise from 0.1 to10 wt. % of an organic or inorganic salt, e.g., a salt selected from thegroup consisting of quaternary ammonium tetrakis phenylborate, dodecylsulfosuccinate, lauryl sulfate, alkyl ether phosphates, benzylkonium,cetylpyrdinium dodecyl sulfosuccinate, lauryl sulfate, alkyl etherphosphates, tetramethylammonium, benzylkonium, cetylpyrdinium, aniodide, a bromide, a perchlorate, a zwitterionic compound,cocamidopropyl hydroxysultaine and quaternary ammonium borate.

The configuration and shape of the first polymer layer and/or the secondpolymer layer may vary widely, but in one embodiment, the continuousfirst polymer layer is substantially circular, preferably domed, and hasa diameter of from about 20 μm to about 2 mm The device may furthercomprise a boundary structure for controlling the spreading of adispensed first polymer layer precursor and/or the second polymer layerprecursor to a predetermined region of the device, e.g., a ringintersecting said first and second electrical contact pads. The firstand second pads optionally are separated by a distance of from about 10μm to about 2 mm.

Another aspect of the invention is to a method of determining deviceusability, comprising: providing a device comprising a first electricalpad; a second electrical pad; and a first polymer layer contacting atleast a portion of the first electrical pad, and a second polymer layercontacting the at least a portion of the second electrical pad and atleast a portion of the first polymer layer. A potential is appliedacross the first and the second electrical pads; an electrical propertyassociated with the first and the second polymer layers is measured andit is determined whether the measured electrical property associatedwith the first and the second polymer layers has exceeded a thresholdlevel associated with the device usability.

Another embodiment of the invention is to a device having a usabilitythreshold comprising a first electrical pad; a second electrical pad; afirst polymer layer contacting at least a portion of the firstelectrical pad; and a second polymer layer contacting at least a portionof the second electrical pad and at least a portion of the first polymerlayer. The first and the second polymer layers have an electricalproperty associated with the device usability threshold.

In a further embodiment, the invention is to a device comprising asensor; a first polymer layer formed on a surface of the device; asecond polymer layer formed on the surface of the device; a firstelectrical pad; and a second electrical pad. The surface comprises thefirst and the second electrical pads positioned adjacent to one anotherand a space there between. The first polymer layer covers at least aportion of the first electrical pad and at least a portion of the spacebetween the pads; the second polymer layer contacts at least a portionof the second electrical pad, at least a portion of the first polymerlayer, and at least a portion of the space therebetween. A preselectedpotential or potential cycle is applied to the first and the secondelectrical pads and impedance or current associated with the first andthe second polymer layers is measured. The measured impedance or currentis converted to a value indicative of an average shelf life timeremaining for other devices from a same manufacturing lot of the device.The surface of the device may be substantially planar.

In another embodiment, the invention is to a method of determiningdevice usability comprising providing a device comprising a firstelectrical pad; a second electrical pad; and a first polymer layercontacting at least a portion of the first electrical pad and a secondpolymer layer contacting at least a portion of the second electrical padand at least a portion of the first polymer layer; applying a potentialacross the first and the second electrical pads; measuring an electricalproperty associated with the first and the second polymer layers;determining a correction factor associated with the measured electricalproperty; and applying the correction factor to a signal generated by asensor to produce a corrected signal. The devices of the inventiontypically have been exposed to different environmental conditions, e.g.,time since manufacture, temperature, ambient conditions or a combinationthereof.

In one aspect, the potential or potential cycle comprises a sigmoidalpotential cycle, a fixed applied potential, a sequence of fixed appliedpotential steps, or a combination thereof. The potential optionallycomprises a potential cycle that is applied at a predetermined frequencyin the range of about 1 Hz to about 100000 Hz. The methods of theinvention optionally include a step of inserting the device into ananalyzer configured to determine whether the measured electricalproperty associated with the first and second polymer layers hasexceeded a threshold level associated with the device usability.

The correction factor preferably is applied to a sensor selected fromthe group consisting of a pH sensor, oxygen sensor, carbon dioxidesensor, hematocrit sensor, glucose sensor, lactate sensor, creatininesensor, sodium sensor, bilirubin, potassium sensor, magnesium sensor,calcium sensor, chloride sensor, inorganic phosphate sensor, liverenzyme sensor, BNP sensor, troponin sensor, BUN sensor, CKMB sensor,NGAL sensor, TSH sensor, D-dimer sensor, PSA sensor, PTH sensor,cholesterol sensor, ALT sensor, AST sensor, prothrombin sensor, APTTsensor, ACT sensor, galectin sensor, CG sensor, and combinationsthereof.

The correction factor preferably is selected from the group consistingof an amperometric correction value, a potentiometric correction value,a coulombic correction value and a conductivity correction value.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be better understood in view of the appendednon-limiting figures, in which:

FIGS. 1 a and 1 b show side and plane views, respectively, of atime-temperature indicator (TTI) device in accordance with oneembodiment of the invention;

FIGS. 1 c and 1 d show side and plane views, respectively, of a TTIdevice in accordance with another embodiment of the invention;

FIGS. 1 e and 1 f show side and plane views, respectively, of a TTIdevice in accordance with another embodiment of the invention;

FIGS. 1 g and 1 h show side and plane views, respectively, of a TTIdevice with a boundary structure in accordance with another embodimentof the invention; and

FIG. 2 presents an image showing a TTI device deposited on first andsecond electrical pads in accordance with aspects of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is best understood in the context of point-of-careblood analysis systems. For example, the shelf life of an i-STAT®cartridge (see the i-STAT® system made by Abbott Point of Care,Princeton, N.J., USA) is typically indicated by a refrigerationexpiration date and a room temperature shelf life that are provided onthe product packaging, e.g., on a fluid-containing pouch thereof. Therefrigeration expiration date defines the length of time that thecartridge may be stored under refrigerated conditions after manufacture,e.g., at about 5° C. Depending on the specific device, the refrigerationexpiration date may be about three months, about six months, about ninemonths or about one year after the date of manufacture. The roomtemperature shelf life defines the length of time that the cartridge maybe stored under room temperature (ambient, e.g., 25° C.) conditionsafter a cartridge or a box of cartridges is removed from refrigerationconditions, i.e., removed from a refrigerator. The room temperatureshelf life should not be allowed to exceed the refrigeration expirationdate. The room temperature shelf life is typically about from two tonine weeks, depending on cartridge type. In practice, the roomtemperature expiration date is calculated from the room temperatureshelf life and is written on the box by the user at the time of removalfrom the fridge. Thus, when a box of cartridges is taken out of therefrigerator, the user typically counts the number of days or months todetermine the room temperature expiration date, verifies that the roomtemperature expiration date does not exceed the refrigeration expirationdate printed on the box or cartridge, and writes the room temperatureexpiration date down on the box. Furthermore, when a cartridge is to beused, the end user again checks the expiry dates. This process lendsitself to potential user error in either or both calculating therefrigeration expiration date and/or verifying that the refrigerationexpiration date has not been passed. The present invention is intendedto facilitate determining the suitability of the cartridge for use,i.e., the non-expiration of the shelf life, automatically taking intoconsideration the age of the device as well as the environment, e.g.,temperature, under which the device has been stored. Thus, the user isrelieved of this task and the opportunity for a user-induced error isdiminished.

While there are several time-temperature or shelf life indicators thatare known in the art, it is highly desirable to keep the cost andcomplexity of the device to a minimum. In the present invention this isachieved by providing (or modifying) a pair of electrical contact pads.Many analytical systems employ electrical or electrochemical principlesand will already have such electrical contact pads as part of thedevice. Consequently, their use adds no cost as they are present andnecessary for other functions, e.g., are used in analyte detection or indevice calibration. The pads are desirably modified so that they can actas time-temperature or shelf life indicators (TTI) while stillfulfilling their intended purpose, typically analyte detection or devicecalibration. Thus, the time-temperature indicator function of theinvention should also be conducted without diminishing the ability orperformance of the contact pads for their primary purpose, e.g., signaltransmission in analyte sensing or device calibration. It is alsocontemplated, however, that the electrical contact pads that are usedfor time/temperature indication according to some embodiments may beseparately provided specifically for performing the role of the TTI, anddo not provide any other role, e.g., in analyte sensing or devicecalibration. In this latter aspect, separate contact pads optionally maybe provided for analyte detection and/or device calibration.

The present invention was in part stimulated by the observation that theelectrical resistance of some prototype ion sensor membrane structureswas found to change after being incubated at an elevated temperature forperiods of time. The present invention is thus based on the changingelectrical properties, e.g., current flow, resistance and the like, of aconnecting material, e.g., connecting layer, comprising at least twopolymers, preferably at least two polymer layers, or the like, that ispositioned between and preferably in electrical contact with twoadjacent contact pads. In one aspect of the invention, at least twopolymers are comprised of different materials, preferably havingdifferent conductivities, and are referred to as a “first TTI material”and “a second TTI material.” Where the TTI materials comprise polymerlayers, they are referred to herein as a “first polymer layer” and a“second polymer layer,” respectively. A connecting material comprisingsuch two different materials is referred to herein as a heterogeneousconnecting material or, where the two different materials are in theform of layers, a heterogeneous connecting layer or simply aheterogeneous layer.

The first and second TTI materials are preferably responsive to theintegral of varying temperature (or other environmental conditions) overtime such that this gives rise to a predictable change of theirelectrical properties. In accordance with aspects of the invention, aTTI relationship between thermal exposure (or other environmentalconditions) and change in electrical property may be established suchthat the electrical property e.g., conductivity or resistance, of theheterogeneous layer depends upon an amount of electrolyte in theheterogeneous layer, e.g., the conductivity or resistance of theheterogeneous layer may depend upon the wt % of the conductive salt inthe heterogeneous layer. For instance, at 10 Hz, a 2% conductive salt,e.g., an electrolyte, may provide a conductance of 0.025 and a 5%conductive salt may provide a conductance of 0.052 (Sm-1) using amixture of 66% trioctyl phosphate (TOP) and 34% polyvinylchloride (PVC).

Devices suitable for use in the present invention include, but are notlimited to, point-of-care devices such as those disclosed in U.S. Pat.No. 7,723,099, the entirety of which is incorporated herein byreference. The devices preferably comprise a first electrical pad and asecond electrical pad in contact with a sensor. As used herein, the term“electrical pad” refers to a location wherein electricity may be appliedto the device. The electrical pads of the present invention maycomprise, for example, a metal contact comprising gold, silver, acombination thereof or another metal. Suitable sensors for use with thepresent invention include, but are not limited to, electrochemicalsensors, amperometric sensors, potentiometric sensors and conductimetricsensors.

The present invention will be specifically described in the context ofan i-STAT cartridge that employs two adjacent hematocrit (Hct) electrodepads, or an Hct pad adjacent to an amperometric sensor pad. Note that,for example, a hematocrit sensor can be used for fluidic integritychecking. Each electrode (or bar) terminates in a contact pad, which isused to make contact with the connector in an i-STAT cartridge reader.Features of the connectors are described in jointly owned U.S. Pat. No.4,954,087, the entirety of which is incorporated herein by reference. Asindicated above, the primary functions of integrity checking andhematocrit measurement should not be affected by the additional use ofthe pads as part of the TTI.

In a first embodiment, the present invention relates to a method ormethods for determining device usability with a TTI. In one embodiment,the method comprises the steps of providing a device comprising a firstelectrical pad, a second electrical pad, and a heterogeneous layercomprising a first TTI material, preferably a first polymer layer, and asecond TTI material, preferably a second polymer layer. The first TTImaterial preferably is more conductive than the second TTI material, orvice versa. The heterogeneous layer electrically contacts at least aportion of the first and second electrical pads. Preferably, the firstand second TTI materials are selected such that they are compatible withone another in the sense that over time and/or at elevated temperatures,the two TTI materials migrate or diffuse into one another causing anincrease in conductivity (or reduction in resistivity) between the firstand second electrical pads. Prior to or at the time of device use, apotential is applied across the first and second electrical pads and anelectrical property associated with the first and second TTI materialsis measured. It is then determined whether the measured electricalproperty associated with the first and second TTI materials has exceededa threshold level associated with device usability.

In some embodiments, as shown in FIGS. 1 a and 1 b, the TTI device 10for determining device usability comprises a heterogeneous layer 15formed in electrical contact with contact pads 20 and 30. The contactpads 20 and 30 may further be in electrical contact with a substrate orbase 40 (optionally a sensor). In accordance with aspects of theinvention, the heterogeneous layer 15 may be formed comprising a firstTTI material 50 and a second TTI material 60.

The first TTI material 50 may be formed by depositing a first TTImaterial precursor 50′ between the contact pads 20 and 30. In oneaspect, the first TTI material precursor 50′ is deposited in contactwith at least a portion of both contact pad 20 and contact pad 30. Thefirst TTI material 50 may comprise a polymer layer, preferably acontinuous polymer layer, and the first TTI material precursor 50′ maycomprise a polymer layer precursor. For example, the first TTI material50 may be formed by depositing, e.g., printing, the TTI materialprecursor 50′, e.g., polymer layer precursor, between and preferablyoverlapping at least a portion of the contact pads 20 and 30, e.g., anamperometric contact pad and a Hct pad or two Hct pads. After depositionof the precursor, the material is preferably dried or cured (e.g., withheat and/or UV radiation) to form the first TTI material 50.

The second TTI material 60 may be formed by depositing a second TTImaterial precursor 60′ onto the first TTI material 50 (after drying orcuring) or onto the first TTI material precursor 50′ (prior to drying orcuring). Preferably, the second TTI material precursor 60′ is depositedwithout contacting contact pads 20 and 30. The second TTI material 60may comprise a polymer layer and the second TTI material precursor 60′may comprise a polymer layer precursor. For example, the second TTImaterial 60 may be formed by depositing, e.g., printing, the second TTImaterial precursor 60′, e.g., polymer layer precursor, onto the firstmaterial precursor 50′ so that the TTI material precursor 60′ does notcontact either contact pad 20 or contact pad 30, e.g., an amperometriccontact pad and a Hct pad or two Hct pads, but the second TTI materialprecursor 60′ contacts either the first TTI material precursor 50′ orthe first TTI material 50 (after drying or curing).

The first TTI material precursor 50′ and the second TTI materialprecursor 60′ are preferably treated, e.g., with heat or otherradiation, dried and/or cured, to form the first TTI material 50 and thesecond TTI material 60, respectively, and forming the heterogeneouslayer 15, in a region between the contact pads 20 and 30, and preferablyoverlapping the contact pads 20 and 30. The precursors may be treatedseparately or together. Preferably, the second TTI material precursor isdeposited on the first TTI material, i.e., after drying or curing of thefirst TTI material precursor, in order to minimize migration ordiffusion of the two TTI materials during device manufacture.Alternatively, the precursors may be sequentially deposited and treatedin a single treating step after they have both been deposited.

In preferred embodiments, one of the first TTI material or the secondTTI material is substantially non-conductive, and the other of the firstTTI material or the second TTI material includes a conductive material.In the embodiment shown in FIGS. 1 a and 1 b, it is preferred that thesecond TTI material 60 is more conductive than the first TTI material50. Thus, for example, the first TTI material 50 may be substantiallynon-conductive, comprising a polymer layer that comprises a polymermatrix and a plasticizer and is substantially free of any conductivematerials, e.g., salts. The second TTI material 60 may similarlycomprise a polymer matrix and a plasticizer, but also preferablycomprises a conductive material, e.g., an organic or inorganic salt. Ofcourse, in an alternative embodiment, the first TTI material may be moreconductive than the second TTI material. In some exemplary embodiments,the two TTI materials have a difference in conductivity of at least2.0×10⁻² S·m⁻¹, e.g., at least 1.7×10⁻² S·m⁻¹ or at least 1.4×10⁻² S·m¹.For example, the first TTI material may have a conductivity of from1.0×10⁻⁵ to 2.0×10⁻⁶ S·m¹, from 2.0×10⁻⁵ to 5.0×10⁻⁶ S·m¹ or from2.0×10⁻⁶ to 5.0×10⁻⁷ S·m¹, and the second TTI material may have aconductivity of from 1.0×10⁻¹ to 2.0×10⁻²S·m¹, e.g., from 5.0×10⁻² to1.7×10⁻² S·m¹ or from 3.3×10⁻² to 1.4×10⁻² S·m¹ in a frequency range of1-10 Hz.

Each of the polymer layers may comprise from 10 to 60 wt. %, e.g., from20 to 40 wt. %, polymer matrix, and from 40 to 90 wt %, e.g., from 60 to80 wt. %, plasticizer. The polymer matrix optionally is selected fromthe group consisting of polyvinylchloride (PVC), polyurethane (PU),polyvinylacetate, carboxylated PVC, hydroxylated PVC andpolydimethylsiloxane (silicon rubber). The plasticizer is optionallyselected from the group consisting of trioctyl phosphate (TOP),nitrophenyloctyl ether (NPOE), bisethylhexylsebacate (BEHS), trimethyltrimellitate (TMTT), dioctyl adipate (DOA) and diisobutyl phthalate(DIBP).

The specific composition of the TTI material precursors, e.g., polymerlayer precursors, that are used to form the TTI materials, e.g., firstand second polymer layers, may vary widely. In an exemplary embodiment,either TTI material precursor comprises the polymer matrix and theplasticizer, as discussed above, but preferably further comprises acarrier medium (e.g., solvent) for imparting the desired physicalproperties for deposition thereof as well as solubilizing the polymercontained therein. In another embodiment, either of the TTI materialprecursors comprises a monomer and an initiator, and polymerization mayoccur after deposition of the TTI material precursor 50′ between thecontact pads 20 and 30 of the sensor 40, e.g., through free radicalpolymerization, optionally with the application of UV radiation.

As indicated above, one of the first and second TTI materials should bemore conductive than the other. As a result, the TTI material precursorcompositions employed should vary in terms of the electrolyte, e.g.,salt, concentration. The precursor to the more conductive TTI material,for example, may further comprise at least 0.1 wt. %, e.g., at least 1.0wt. % or at least 10 wt. % of a salt, e.g., an organic salt, to impartconductivity thereto. In terms of ranges, the precursor to the moreconductive TTI material may comprise from 0.5 to 10 wt. %, e.g., from 3to 15 wt. % or from 10 to 50 wt. % of a salt, e.g., an organic salt.Conversely, the precursor to the less conductive TTI material, forexample, may comprise less than 0.01 wt. %, e.g., less than 0.1 wt. % orless than 1.0 wt. % of a salt, e.g., an organic salt.

The specific composition of the more conductive precursor, e.g., secondTTI material precursor 60′ that is used to form the second TTI material60, may similarly vary widely. In an exemplary embodiment, the moreconductive precursor, e.g., the second TTI material precursor 60′,comprises the polymer matrix, the plasticizer, and the salt, asdiscussed above, but preferably further comprises a carrier medium(e.g., solvent) for imparting the desired physical properties fordeposition thereof as well as solubilizing the polymer containedtherein. In another embodiment, the more conductive TTI materialprecursor comprises a salt, a monomer and an initiator, andpolymerization occurs onto the surface of the less conductive materialor material precursor, e.g., through free radical polymerization,optionally with application of UV radiation. The deposition andpolymerization of the first and second TTI material precursors may beconducted in any desired sequence or simultaneously, as discussed above.

The carrier medium for either precursor may comprise water or an organicsolvent. As these materials are preferably microdispensed onto thecontact pads 20 and 30 using microdispensing methods and equipment asdescribed in jointly owned U.S. Pat. No. 5,554,339, previouslyincorporated herein by reference, similar considerations as toingredients, viscosity, surface preparation and pretreatment and thelike also apply to the present invention.

As discussed, one of the TTI materials should be more conductive thanthe other of the TTI materials. The second TTI material 60, for example,may be substantially conductive. For example, the second TTI material 60preferably comprises a polymer layer (preferably a continuous polymerlayer), a polymer matrix, a plasticizer, and an electrolyte (e.g., asalt). In a preferred embodiment, the second polymer layer comprisesfrom 10 to 60 wt. %, e.g., from 20 to 40 wt. %, polymer matrix, from 40to 90 wt %, e.g., from 60 to 80 wt. %, plasticizer, and from 0.05 to 20wt. %, e.g., from 0.1 to 10 wt. %, salt. The polymer matrix optionallyis selected from the group consisting of polyvinylchloride (PVC),polyurethane (PU), polyvinylacetate, carboxylated PVC, hydroxylated PVCand polydimethylsiloxane (silicon rubber). The plasticizer is optionallyselected from the group consisting of trioctyl phosphate (TOP),nitrophenyloctyl ether (NPOE), bisethylhexylsebacate (BEHS), trimethyltrimellitate (TMTT), dioctyl adipate (DOA) and diisobutyl phthalate(DIBP).

The electrolyte, e.g., salt, selected for the conductive material ispreferably highly lipophilic so as to enhance polymer solubility and canbe either organic or inorganic. Exemplary organic salts may be selectedfrom the group consisting of dodecyl sulfosuccinate, lauryl sulfate,alkyl ether phosphates, tetramethylammonium salts, benzalkonium salts,cetylpyridinium salts and zwitterionic organic salts, e.g.,cocamidopropyl hydroxysultaine. Exemplary inorganic salts may beselected from the group consisting of iodide, bromide, perchlorate andzwitterionic inorganic salts. In a preferred embodiment, the saltcomprises quaternary ammonium borate.

As illustrated in FIGS. 1 a and 1 b, as time increases from the date ofmanufacture of the device 10 and/or as temperature increases, theelectrolyte (e.g., a salt) may diffuse 70 out of the more conductivesecond TTI material 60 and into the less conductive first TTI material50 such that the conductivity of the first TTI material 50 increasesover time and/or temperature. In some embodiments, a potential orpotential cycle 80 may be used to take an initial measurement at thedate of manufacture, which may indicate a high initial impedance valuethat would decrease as the electrolyte further diffuses 70 from thesecond TTI material 60 into the first TTI material 50 resulting in anincrease in conductivity of the first TTI material 50.

In an alternative embodiment, shown in FIGS. 1 c and 1 d, a first TTImaterial 150 may be formed by depositing a first TTI material precursor150′ between contact pads 120 and 130 and over a second TTI material 160or second TTI material precursor 160′. Preferably, the first TTImaterial is more conductive than the second TTI material, although thereverse is also contemplated. In accordance with this aspect, the secondTTI material 160 may be formed prior to formation of the first TTImaterial 150 by depositing a second TTI material precursor 160′ betweenthe contact pads 120 and 130 on a surface of TTI device 110. Preferably,the second TTI material precursor 160′ is deposited not in contact withthe contact pads 120 and 130. The second TTI material 160 may comprise apolymer layer that includes a conductive material, e.g., a salt, and thesecond TTI material precursor 160′ may comprise a polymer layerprecursor and the electrolyte. For example, the second TTI material 160may be formed by depositing, e.g., printing, and drying and/or curingthe second TTI material precursor 160′, e.g., polymer layer precursor,onto a surface of the TTI device 110 so that the second TTI materialprecursor 160′ does not contact the contact pads 120 and 130, e.g., anamperometric channel pad and a Hct pad or two Hct pads.

Preferably, the first TTI material precursor 150′ is deposited over thesecond TTI material or the second TTI material precursor and in contactwith contact pads 120 and 130. The first TTI material 150 may comprise apolymer layer and the first TTI material precursor 150′ may comprise apolymer layer precursor. For example, the first TTI material 150 may beformed by depositing, e.g., printing, drying and/or curing the first TTImaterial precursor 150′, e.g., polymer layer precursor, between andpreferably overlapping contact pads 120 and 130, e.g., an amperometricchannel pad and a Hct pad or two Hct pads, such that the first TTImaterial precursor 150′ substantially covers the second TTI material 160or the second TTI material precursor 160′.

In one aspect, the first TTI material precursor 150′ and the second TTImaterial precursor 160′ are treated, e.g., with heat or other radiation,dried and/or cured, together or separately, to form the first TTImaterial 150 and the second TTI material 160 respectively. In thismanner, a heterogeneous layer is formed in a region between contact pads120 and 130, and preferably overlapping the contact pads 120 and 130, sothat the first TTI material 150 contacts at least a portion of the firstand second contact pads and the second TTI material 160 does not contacteither contact pad.

As illustrated in FIGS. 1 c and 1 d, as time and/or temperatureincreases, the electrolyte (e.g., a salt) may diffuse 170 out of thesubstantially conductive second TTI material 160 and into thesubstantially non-conductive first TTI material 150, such that the firstTTI material 150 increases in conductivity. A potential or potentialcycle 180 may be used in measuring an electrical property associatedwith the heterogeneous layer, e.g., the first and second TTI materials150 and 160, as the electrolyte diffuses 170 out of the second TTImaterial 160 and into the first TTI material 150, thereby increasing theconductivity of the first TTI material 150.

In another embodiment, shown in FIGS. 1 e and 1 f, a first TTI material250 may be formed by depositing a first TTI material precursor 250′between contact pads 220 and 230, but in contact with only one of thecontact pads. Thus, the first TTI material precursor 250′ may bedeposited in contact with only one of the contact pads 220 and 230 andforming a space between the TTI material precursor 250′ and the other ofthe two contact pads 220 and 230. The first TTI material precursor maythen be dried and/or cured to form the first TTI material. As shown,first TTI material 250 contacts contact pad 220, but is not inelectrical contact with contact pad 230.

The second TTI material 260 may be formed by depositing a second TTImaterial precursor 260′ between contact pads 220 and 230, but in contactwith the first TTI material 250 or first TTI material precursor 250′ andthe contact pad that is not in contact with first TTI material 250 orfirst TTI material precursor 250′. The second TTI material precursor maythen be dried and/or cured to form the second TTI material. As describedabove, the second TTI material 260 preferably is more conductive thanthe first TTI material 250, although the reverse is also contemplated.The first and second TTI precursors may be treated, dried and/or cured,e.g., with heat or other radiation, separately or simultaneously, toform the first TTI material 250 and the second TTI material 260,respectively, and thereby forming a heterogeneous layer.

As illustrated in FIGS. 1 e and 1 f, as time and/or temperatureincreases, the electrolyte (e.g., a salt) may diffuse 270 out of thesubstantially conductive second TTI material 260 and into thesubstantially non-conductive first TTI material 250 such that theconductivity of the first TTI material 250 increases. A potential orpotential cycle 280 may be used in measuring an electrical propertyassociated with the first and second TTI materials 250 and 260 as theelectrolyte diffuses 270 out of the second TTI material 260 and into thefirst TTI material 250 in order to determine device usability.

The first and second TTI materials preferably are accurately positionedin the devices in order, for example, to avoid potential contaminationof the connector, e.g., connector pins, in the instrument. Notably, thetransfer of polymeric material from the first and second TTI materialsto the connector pins should be minimized or avoided. Consequently, insome aspects, as shown in FIGS. 1 g and 1 h, the present invention alsorelates to devices 310 having a boundary structure 390 that facilitatescontrolling the spreading of the dispensed first and second precursors350′ and 360′ that form the first and second TTI materials 350 and 360,e.g., the heterogeneous layer 315. The boundary structure 390 may, forexample, be positioned at a predetermined region of the device 310, forexample as a polygon, e.g., square, pentagon, hexagon, octagon, and thelike, or as a cylindrical or ring shape. This boundary structure 390, ifemployed, preferably is positioned in a manner that intersects the twoadjacent pads 320 and 330.

The boundary structure 390 may be formed, for example, by patterning aridge of passivation material, e.g., a photoformable passivationmaterial, such as a photoformable polyimide. The photoformablepassivation material may be spin-coated and patterned to form aninsulating layer over the contact lines on the chip. Thus, the mask forthat process may also include the ring structures. Jointly owned U.S.Pat. No. 5,200,051, the entirety of which is incorporated by reference,discloses similar processes and photoformable materials. Otherphotoformable materials, e.g., those based on polyvinyl alcohol orBichromated gelatin, may also be used.

In the above-described embodiments, connector pin tips may initiallycontact a top portion of the contact pads and move slightly towards amiddle of the chip as a connector applies more force. Accordingly, it ispreferred that the boundary structure 390, e.g., ring, be used for firstand second TTI material positions that are closer to the middle of thechip in order to properly locate the heterogeneous layer. In thismanner, the TTI material preferably is positioned beyond the extent oftravel of the pin tip, thus obviating the contamination issue. Forexample, the scratch marks 410 in the middle of the contact pads 420 and430 in FIG. 2 show where the connector pins have hit the contact padsand moved during connector engagement in relationship to boundarystructure 440.

In the above-described embodiments, the step of depositing, e.g.,printing, the first and second TTI material precursors between the twocontact pads may be accomplished by using a microdispensing process suchas the one described in jointly owned U.S. Pat. No. 5,554,339, theentirety of which is incorporated herein by reference. This processinvolves preparing a fluid composition suitable for forming the polymerlayer and loading it into a microsyringe assembly. The microsyringeassembly may comprise, for example, a reservoir, a microsyringe needle,a pump for delivering the TTI material precursor from the reservoir tothe microsyringe needle, and a multidirectional controller so thatdroplets may be brought into contact with the area between the contactpads. Automatic alignment of the needle tip to the dispensing locationmay be achieved in manufacturing, for example, using an opticalrecognition system using one or more fiduciary marks.

In a preferred embodiment, particularly for low-cost compatiblemanufacturing methods, the process of depositing the TTI materialprecursor may be substantially similar to the printing process that isemployed for the manufacture of sensing membranes onto electrodes (see,e.g., U.S. Pat. No. 5,554,339) and the printing of reagents ontosurfaces or conduit walls of cartridge components for subsequentdissolution into a blood sample.

As described above, the heterogeneous layer is preferably formed bymicrodispensing one or more drops of the first and second TTI materialprecursors onto the TTI device and removing the carrier medium,optionally with heat, and/or drying the precursor to form the first andsecond TTI materials. In a preferred embodiment, e.g., for theembodiments described herein, the deposited first and second TTImaterial precursors form a substantially circular shape having adiameter in the range of from about 20 μm to about 2 mm, preferably 100μm to 500 and are generally domed, covering, as required, the distancebetween the two pads, which preferably is in the range of from about 10μm to 1 mm, preferably from about 10 μm to 200 μm. The average thicknessof the heterogeneous layer is generally in the range of from about 1 μmto about 200 μm, preferably from about 20 μm to about 60 One skilled inthe art will appreciate that ranges outside of those provided above maybe employed, for example, for larger sensor devices such as some homeuse glucose testing strips.

The above-described configurations of a TTI device enable a readerinstrument (e.g., an analyzer) to measure an electrical property of thefirst and second TTI materials before any sample or calibrant fluidcontacts the electrodes, which are located in a fluid conduit within thecartridge. See, for example, jointly owned U.S. Pat. Nos. 5,096,669 and7,491,821, the entireties of which are incorporated herein by reference.In embodiments, the electrical property measured may include current,resistance, impedance, conductivity, or a combination thereof. In apreferred embodiment, the electrical property that is measured is theopen circuit resistance (R_(TTI)) of the first and second TTI materials.If the electrical property, e.g., R_(TTI) measurement, does not exceed apredetermined threshold value or is within a certain range, thecartridge is considered valid for use. For such cartridges, depending onhow an analyzer is programmed, the analyzer may indicate that thecartridge has expired or otherwise reject the cartridge and abort thetest cycle, or engage in another remedial action, e.g., sensor outputcorrection, as discussed in greater detail herein. Nevertheless, itshould be understood, however, that such devices may still be suitablefor use but may not have the desired degree of clinical precision.

The present invention advantageously avoids the need to add conductiveparticles, e.g., carbon black, conductive carbon nanotubes, metallicparticles, metallic oxide, semi-conductor particles, etc, to the firstand second TTI materials in order to adjust an initial resistivity ofthe heterogeneous layer to a desired level. By contrast, the presentinvention, in some aspects, relies on the second TTI material comprisinga polymer, e.g., a conductive material, and various other molecularspecies (e.g., an electrolyte). While these other molecular species maybe polar or ionic and thus affect the substantial conductivity of thesecond TTI material, they are not particulate in nature. In a preferredembodiment, lipophilic organic ammonium ion salts are used, e.g.,dodecylammonium chloride and tetraphenylborate to impart the desireddegree of resistivity/conductivity. Nevertheless, in other aspects ofthe invention, such conductive particles may be included in theconductive TTI material or conductive TTI material precursor used in thedevices and methods of the invention.

While the present invention is conceived in a first embodiment as aprocess for determining device usability, in a second embodiment, theinvention may be used for sensor correction. Thus, in the firstembodiment, for example, the invention is to a TTI device configured fordetermining device usability comprising first and second TTI materials,e.g., a heterogeneous layer, formed on a surface of the TTI device,wherein the surface comprises two adjacent electrical contact pads. Asindicated above, the first and second TTI materials preferably cover atleast a portion of the two electrical contact pads and at least aportion of the space on the surface between the contact pads. In apreferred embodiment, a preselected potential or potential cycle isapplied to the pads and the impedance (Z) or current (1) associated withthe (combined) first and second TTI materials as a heterogeneous layeris measured, and the resulting measured value is compared with apredetermined threshold value to determine whether the device is usable.

The invention may also be used to determine the average shelf life ofsimilarly aged and stored devices, e.g., devices from the samemanufacturing lot. Thus, in another embodiment, the invention is to adevice having a usability threshold and including a sensor and first andsecond TTI materials, e.g., included in a heterogeneous layer, formed ona surface of a TTI device, wherein the surface may be substantiallyplanar and comprises two adjacent electrical contact pads having a spacetherebetween. The first and second TTI materials cover at least aportion of the two electrical contact pads and a portion of the space onthe surface between the contact pads. In operation, a preselectedpotential or potential cycle is applied to the contact pads and anelectrical property, e.g., impedance or current, associated with thefirst and second TTI materials is measured. The measured value isconverted to a value indicative of an average shelf life time remainingfor other devices from the same manufacturing lot as the device signalfrom the output of the sensor to provide a corrected sensor signal.

In a related embodiment, the invention is to a method of correcting asignal in a sensing device, comprising the steps of: (a) providing asensing device comprising a sensor, a first electrical pad, a secondelectrical pad, and first and second TTI materials, e.g., included in aheterogeneous layer, contacting at least a portion of the first andsecond electrical pads; (b) applying a potential across the first andsecond electrical pads; (c) measuring an electrical property associatedwith the first and second TTI materials (heterogeneous layer); (d)determining a correction factor associated with the measured electricalproperty, e.g., from a look up table or the like; and (e) applying thecorrection factor to a signal generated by the sensor to produce acorrected signal.

In order to determine the appropriate correction factor, e.g., from alook up table or correction algorithm, it is necessary to establish arelationship between the electrical property and the correction factors.Thus, in another embodiment, the invention is to a method of determininga correction factor comprising the steps of: (a) providing a pluralityof devices, each of the devices comprising a sensor; a first electricalpad; a second electrical pad; and a heterogeneous layer contacting atleast a portion of the first and second electrical pads, wherein thedevices have been exposed to different environmental conditions; (b)measuring an electrical property of the heterogeneous layer for each ofthe devices; (c) measuring a sensor signal for a control fluid, asdefined below, for each of the devices; and (d) correlating the measuredelectrical properties with the measured sensor signals for the pluralityof devices to determine the correction factor.

In a more generalized embodiment, the invention is to a device havingfirst and second TTI materials, e.g., included in a heterogeneous layer,formed on a surface, wherein the surface comprises two adjacentelectrical contact pads. The first and second TTI materials cover atleast a portion of the two electrical contact pads and a portion of thespace on the surface between the pads. When a preselected potential orpotential cycle is applied to the two contact pads and an electricalproperty, e.g., impedance or current, associated with the first andsecond TTI materials is measured, the measured value determines whetherthe device is usable and, if the device is usable, whether it isnecessary to correct the signal. If it is necessary to correct thesignal, the device may determine the appropriate correction factor andmodify a sensor signal from the device based on the correction factor toprovide a corrected signal. For example, a portion of a manufacturinglot of devices can be tested under different storage conditions andtested with a standard liquid of known composition (control fluid). Ifthe TTI value and control fluid values are recorded, any variationbetween the expected and measured control fluid value can be correlatedwith the TTI value and a correction algorithm created. This can then beimplemented in the instrument when running real samples with thatmanufacturing lot of devices.

In accordance with aspects of the invention, various potential cyclesmay be used in measuring the electrical property associated with thefirst and second TTI materials, e.g., the heterogeneous layer. In someexemplary embodiments, the potential cycle may be selected from asigmoidal potential cycle, a fixed applied potential, and a potentialthat is a sequence of fixed applied potential steps. Measurements may bemade, for example, with an impedance measuring circuit in an instrument,or a current measuring circuit in an instrument. In one embodiment, aninitial current value associated with the heterogeneous layer ismeasured when the device is manufactured and the threshold level is atleast three times, preferably at least five times, greater than theinitial current value. Conversely, in another aspect, an initialimpedance value associated with the heterogeneous layer is measured whenthe device is manufactured and the threshold level is at least threetimes less, preferably at least five times less, than the initialimpedance. In some exemplary embodiments where current is measured, thecurrent ranges from picoamps to milliamps, but more typically fromnanoamps to microamps, e.g., from 0.1 to 100 nanoamps. Where impedanceis measured, the typical impedance may range, for example, from belowthe megaohm range to above the gigaohm range, more typically in the tensof megaohms to low gigaohm range, optionally from 100 to 1500 megaohmsat a frequency of from about 1 to about 10 Hz.

Where a sensor correction is made, the correction value may be selectedfrom an amperometric correction value, a potentiometric correctionvalue, a coulombic correction value and a conductivity correction value.These values are typically applied to a sensor selected from the groupconsisting of a pH sensor, oxygen sensor, carbon dioxide sensor,hematocrit sensor, glucose sensor, lactate sensor, creatinine sensor,sodium sensor, potassium sensor, magnesium sensor, calcium sensor,chloride sensor, phosphate sensor, liver enzyme sensor, BNP sensor,troponin sensor, BUN sensor, CKMB sensor, NGAL sensor, TSH sensor,D-dimer sensor, PSA sensor, PTH sensor, cholesterol sensor, ALT sensor,AST sensor, prothrombin sensor, APTT sensor, ACT sensor, galectinsensor, and combinations thereof.

The present invention may be easily adaptable to widely availablecommercial technologies and can be performed with existing electronicsthat require no hardware changes but only a software modification, whichare generally simpler to implement than hardware modifications. Forexample, an i-STAT instrument may be able to measure conductivity at 10kHz and 50 kHz, but may be conveniently expanded to a wider frequencyrange. In a preferred embodiment, this circuitry is programmed tomeasure the electrical resistance between adjacent contact pads at afrequency of 10 Hz. It is believed that low frequency impedancemeasurements in the range of from about 1 Hz to about 100 Hz are mostsensitive in detecting a change in the electrical property of theheterogeneous layer. Without being bound by theory, it is understoodthat changes in circuit impedance may be due to a change in the bulkmembrane resistance, which is best observed when the ions in themembrane migrate some distance so they must be under a polarizingvoltage for some time, which requires a low frequency. One possiblemechanism is that at higher frequencies, the voltage oscillates soquickly that the ions do not migrate appreciably. As a result, theresistance to their movement does not influence the impedance. Anotherpossibility is that the impedance change over time that is observed inthe present invention may be contributed in part by the electrodeoxidation and its interface with the bulk polymer membrane. In general,electrode polarization impedance becomes more significant at lowerfrequencies than at higher frequencies. In any event, an importantparameter to the present invention is an empirically observable andconsistently predictable change in the electrical property.

To avoid compromising the use of the contact pads for their primaryfunction, typically analyte sensing, where the electrical property thatis measured is the open circuit resistance, the R_(TTI) preferably ismuch greater than, e.g., at least 1000 times greater than, the closedcircuit resistance, i.e., the resistance measured between the electrodesattached to the contact pads with either sample or calibrant fluidcovering the electrodes. However, the R_(TTI) preferably is much lower,e.g., at least 100 times lower, than the existing open circuitresistance, i.e., the resistance between the contact pins prior tocontacting the pads. This goal may be accomplished through carefuldesign of the geometry of the heterogeneous layer and control of thefirst and second TTI material compositions. Thus, a reducedcross-sectional polymer layer area and an extended polymer path lengthbetween the pads will generally lead to an increased resistance for anygiven material composition, whereas increasing the ionic content and ionmobility of the polymer layer for a given geometry will generally leadto a decreased resistance. Note that the typical sample or calibrantfluid resistance is in the range of about ten to thousands of ohms,whereas the open circuit resistance is generally greater than severalgiga-ohms. Thus, the TTI resistance is preferably in the mega-ohm to lowgiga-ohm range.

In embodiments, a quantitative relationship between R_(TTI) and actualaging of a test cartridge is established. As indicated herein, theobjective is to prevent expired cartridges from being used and preventusable cartridges from being discarded. Thus, in another embodiment, theinvention is to a method of determining a threshold level associatedwith analytical device usability. The method comprises the steps of: (a)providing a plurality of devices, each of the devices comprising asensor; a first electrical pad; a second electrical pad; and aheterogeneous layer contacting at least a portion of the first andsecond electrical pads, wherein the devices have been exposed todifferent environmental conditions; (b) measuring an electrical propertyof the heterogeneous layer for each of the devices; (c) measuring asensor signal for a control fluid for each of the devices; (d)identifying a subset of the plurality of devices that provide a signalhaving a predetermined acceptable precision level for the control fluid;and (e) determining the threshold level that corresponds to theelectrical property of the heterogeneous layer for the subset of theplurality of devices.

In accordance with aspects of the invention, the invention has theadvantage that it enables a sensor that would otherwise have beenconsidered to have exceeded its shelf life to still be used based on atime and temperature integrated correction factor. For example, once theTTI relationship between thermal exposure (or other environmentalconditions) and change in electrical property, e.g., impedance, has beenestablished, a dynamic correction algorithm can be created and embeddedinto the instrument software to generate the correction factor.

An approach to correcting an assay result for aging may rely upon thefollowing. The assay and TTI need to predictably change when subjectedto the same thermal stress independent of the conditions to which it hasbeen subjected. For example, an assay storage condition with highlyfluctuating temperature (bounded by the allowable extremes) shouldproduce nearly the same change as is observed when the assay is storedat a fixed temperature. If this condition is met, and if the time andmean kinetic temperature (MKT), which is the equivalent fixedtemperature at which an assay would need to be held to reach the samedegree of aging, are known then the assay result can be corrected. Ifthe duration of thermal stress is known (ideally the time since the dateof manufacture), the TTI can be used to calculate the MKT. Based uponthe relationship established between the MKT and the change in the assayresult, the expected change can be back calculated from the result. Thecorrection algorithm may be derived using an Arrhenius model. Forexample, a correction factor for creatinine may be determined by thefollowing formula:

[Crea]=b*response−c

wherein:

“response” is a slope of the sensor response (e.g., current) for thesample;

(b) is a calibration parameter for slope (b) of the sensor response;

(c) is a calibration parameter for intercept (c).

With aging, the response slope b is changing according to Arrheniusmodel and creatinine concentration can be corrected as follows:

$\lbrack{CREA}\rbrack = {{\frac{b}{{\theta_{1} \cdot {\exp ( {{- ( {\theta_{2} \cdot {\exp ( {{- \frac{{Ea}_{CREA}}{R}} \cdot ( {\frac{1}{MKT} - \frac{1}{T_{ref}}} )} )}} )} \cdot {time}} )}} + \theta_{3}} \times {Response}} + c}$

wherein:

MKT is the mean kinetic temperature and can be estimated from themeasured TTI impedance R_(TTI);

Ea_(CREA) is apparent activation energy for change in creatinine sensorresponse;

R is the universal gas constant;

T_(ref) is the experimental reference temperature;

θ₁ is a pre-exponential factor for time/temperature changes in b;

θ₂ is the rate of change in b at T_(ref); and

θ₃ is non-temperature dependent offset=1−θ₁.

By utilizing the present invention it is possible to significantlyfurther extend the time available for typical room temperature storageof blood testing devices. In this context, the improvement can be atleast about 50%. In addition, the invention may be applied to anyelectrochemical test device where the instrumentation enables current orimpedance measurements, e.g., glucose meters used for diabetesmonitoring with electrochemical sensor strips. The invention alsosimplifies the process of implementing point of care testing technologyfor the user, e.g., nurse, doctor or other healthcare professional. Italso ensures that test devices, e.g., cartridges, strips and the like,have been stored properly prior to the use of each individual device. Itcan be used to compensate for device aging factors and improve theaccuracy of results throughout the life of the device.

In another embodiment of the present invention, the measured value fromthe TTI is used to calculate the remaining percentage of thermal stress(or other environmental stressors) for the rest of a manufacturing lotof the same devices stored under the same conditions. This isessentially the length of time for room temperature storage that remainsfor all of the other devices that were stored with the tested device buthave yet to be used. As all of the devices in a given lot (e.g., a giveni-STAT cartridge manufacturing lot) are manufactured in the same way andat the same time, the tested device gives a measured impedance orcurrent value that not only is relevant to that particular device (asapplied in other disclosed embodiments) but can also be usedpredicatively with respect to other devices from the same manufacturedlot that have been subjected to the same storage conditions as thetested device.

For example, assuming a thermal stress budget of 100% at the time thelot of cartridges are removed from refrigeration, at the time aparticular cartridge is tested, it is possible to calculate from themeasured TTI value that some fraction of the budget remains, i.e., avalue from 100% to 0% (expiry). This is based on an embedded data curvereflecting this range that is part of the instrument software algorithm.The curve is derived from the type of data shown in the various figures,i.e., factory determined and uploaded to the instrument forpredetermined lots.

Optionally, this information is displayed on the instrument and relayedto the hospital's point of care coordinator. This enables a new supplyof devices, e.g., a new box of cartridges, to be ordered when expiry isimminent. It also enables the creation of a cartridge management reportthat allows the point of care coordinator to easily monitor and managecartridges throughout a facility in a remote manner. Note that inpractice, individual cartridges are generally traceable to a particularbox and it is a reasonable assumption that cartridges are storedtogether in the box. Consequently, every time a cartridge is run from aparticular box it provides useable information on the amount of roomtemperature storage for the remaining cartridges in that box and allboxes stored similarly.

While the invention has been described in terms of various preferredembodiments, those skilled in the art will recognize that variousmodifications, substitutions, omissions and changes can be made withoutdeparting from the spirit of the present invention. Accordingly, it isintended that the scope of the present invention be limited solely bythe scope of the following claims.

1. A method of determining device usability, comprising the steps of:providing a device comprising a first electrical pad; a secondelectrical pad; and a first polymer layer contacting at least a portionof said first and said second electrical pads and a second polymer layercontacting said first polymer layer and not said first and said secondelectrical pads; applying a potential across said first and said secondelectrical pads; measuring an electrical property associated with saidfirst and said second polymer layers; and determining whether themeasured electrical property associated with said first and said secondpolymer layers has exceeded a threshold level associated with saiddevice usability.
 2. The method of claim 1, wherein said first polymerlayer comprises a polymer matrix and a plasticizer.
 3. The method ofclaim 2, wherein said second polymer layer comprises a polymer matrix, aplasticizer, and an organic salt.
 4. The method of claim 3, wherein saidfirst and said second polymer layers each comprise from 20 to 40 wt. %polymer matrix.
 5. The method of claim 4, wherein said polymer matrix ineach layer comprises a polymer selected from a group consisting ofpolyvinyl chloride, polyurethane, polyvinylacetate, carboxylated PVC,hydroxylated PVC and polydimethyl siloxane.
 6. The method of claim 5,wherein said first and said second polymer layers each comprise from 60to 80% plasticizer.
 7. The method of claim 6, wherein said plasticizerin each layer is selected from a group consisting of trioctyl phosphate(TOP), nitrophenyloctyl ether (NPOE), bisethylhexylsebacate (BEHS),trimethyl trimellitate (TMTT), dioctyl adipate (DOA) and diisobutylphthalate (DIBP).
 8. The method of claim 7, wherein said second polymerlayer comprises from 0.1 to 10 wt. % of an organic salt.
 9. The methodof claim 7, wherein said second polymer layer comprises a salt selectedfrom the group consisting of quaternary ammonium tetrakis phenylborate,dodecyl sulfosuccinate, lauryl sulfate, alkyl ether phosphates,benzylkonium, cetylpyrdinium dodecyl sulfosuccinate, lauryl sulfate,alkyl ether phosphates, tetramethylammonium, benzylkonium,cetylpyrdinium, an iodide, a bromide, a perchlorate, a zwitterioniccompound, cocamidopropyl hydroxysultaine and quaternary ammonium borate.10. The method of claim 1, wherein said first polymer layer issubstantially circular and has a diameter of from about 20 μm to about 2mm.
 11. The method of claim 1, wherein said second polymer layer issubstantially circular and has a diameter of from about 20 μm to about 2mm, and wherein the diameter is less than the first polymer layer. 12.The method of claim 1, wherein said device further comprises a boundarystructure for controlling the spreading of a dispensed first polymerlayer precursor to a predetermined region of said device.
 13. The methodof claim 1, wherein said device further comprises a boundary structurefor controlling the spreading of a dispensed second polymer layerprecursor to a predetermined region of the device.
 14. The method ofclaim 1, wherein said first and said second pads are separated by adistance of from about 10 μm to about 2 mm.
 15. The method of claim 1,wherein said first and said second polymer layers are domed.
 16. Themethod of claim 1, wherein said electrical property comprises current,resistance, impedance, conductivity, or a combination thereof.
 17. Themethod of claim 16, further comprising measuring an initial currentvalue associated with said first and said second polymer layers whensaid device is manufactured and wherein said threshold level is at leastfive times greater than said initial current value.
 18. The method ofclaim 16, further comprising measuring an initial impedance valueassociated with said first and said second polymer layers when saiddevice is manufactured, wherein said threshold level is at least fivetimes less than said initial impedance.
 19. The method of claim 1,wherein said potential comprises a sigmoidal potential cycle, a fixedapplied potential, a sequence of fixed applied potential steps, or acombination thereof.
 20. The method of claim 1, wherein said potentialcomprises a potential cycle that is applied at a predetermined frequencyin the range of about 1 Hz to about 100000 Hz.
 21. The method of claim1, further comprising inserting said device into an analyzer configuredto determine whether said measured electrical property associated withsaid first and said second polymer layers has exceeded said thresholdlevel associated with said device usability.
 22. The method of claim 1,where said device further comprises a sensor selected from a groupconsisting of a pH sensor, oxygen sensor, carbon dioxide sensor,hematocrit sensor, glucose sensor, lactate sensor, creatinine sensor,sodium sensor, potassium sensor, chloride sensor, calcium sensor, BNPsensor, troponin sensor, CKMB sensor, NGAL sensor, TSH sensor, D-dimersensor, PSA sensor, PTH sensor, cholesterol sensor, ALT sensor, ASTsensor, prothrombin sensor, APTT sensor, ACT sensor, galectin sensor,and combinations thereof
 23. A method of claim 1, where said firstpolymer layer is printed onto said device in a first step and saidsecond polymer layer is printed onto said first layer in a second step.24. A method of claim 1, where said second polymer layer is printed ontosaid device in a first step and said first polymer layer is printed ontosaid device and covering said second layer in a second step.
 25. Amethod of claim 1, where said electrical response is dependent on anorganic salt migrating from said second polymer layer into said firstpolymer layer, wherein said migration is time and temperature dependent.26. A device having a usability threshold, comprising: a firstelectrical pad; a second electrical pad; a first polymer layerelectrically contacting at least a portion of said first and said secondelectrical pads; and a second polymer layer contacting said firstpolymer layer and not contacting said first and said second electricalpads, wherein said first and said second polymer layers have anelectrical property associated with said device usability threshold. 27.A device comprising: a sensor; a first polymer layer formed on a surfaceof said device; a second polymer layer formed on said first polymerlayer; a first electrical pad; and a second electrical pad, wherein:said surface comprises said first and said second electrical padspositioned adjacent to one another and a space therebetween; said firstpolymer layer covers at least a portion of said first and said secondelectrical pads and a portion of said space therebetween; said secondpolymer layer contacts said first polymer layer and not said first andsaid second electrical pads; a preselected potential or potential cycleis applied to said first and said second electrical pads and animpedance or current associated with said first and said second polymerlayers is measured; and said measured impedance or current is convertedto a value indicative of an average shelf life time remaining for otherdevices from a same manufacturing lot of said device.
 28. A method ofdetermining device usability, comprising the steps of: providing adevice comprising a first electrical pad; a second electrical pad; and afirst polymer layer contacting at least a portion of said first and saidsecond electrical pads and a second polymer layer contacting said firstpolymer layer and not said first and said second electrical pads;applying a potential across said first and said second electrical pads;measuring an electrical property associated with said first and saidsecond polymer layers; and determining a correction factor associatedwith said measured electrical property; and applying said correctionfactor to a signal generated by a sensor to produce a corrected signal.29. The method of claim 28, wherein said correction factor is selectedfrom a group consisting of an amperometric correction value, apotentiometric correction value, a coulombic correction value and aconductivity correction value.
 30. The method of claim 28, wherein saidsensor is selected from a group consisting of a pH sensor, an oxygensensor, a carbon dioxide sensor, a hematocrit sensor, a glucose sensor,a lactate sensor, a creatinine sensor, a sodium sensor, a potassiumsensor, a chloride sensor, a calcium sensor, a BNP sensor, a troponinsensor, a CKMB sensor, a NGAL sensor, a TSH sensor, a D-dimer sensor, aPSA sensor, a PTH sensor, a cholesterol sensor, an ALT sensor, an ASTsensor, a prothrombin sensor, an APTT sensor, an ACT sensor and agalectin sensor.
 31. The method of claim 28, wherein said first polymerlayer comprises a polymer matrix and a plasticizer.
 32. The method ofclaim 31, wherein said second polymer layer comprises a polymer matrix,a plasticizer, and an organic salt.
 33. The method of claim 32, whereinsaid electrical property comprises current, resistance, impedance,conductivity, or a combination thereof.
 34. The method of claim 33,further comprising measuring an initial current value associated withsaid first and said second polymer layers when said device ismanufactured and wherein said threshold level is at least five timesgreater than said initial current value.
 35. The method of claim 33,further comprising measuring an initial impedance value associated withsaid first and said second polymer layers when said device ismanufactured, wherein said threshold level is at least five times lessthan said initial impedance.
 36. The method of claim 28, wherein saidpotential comprises a sigmoidal potential cycle, a fixed appliedpotential, a sequence of fixed applied potential steps, or a combinationthereof.
 37. The method of claim 28, wherein said potential comprises apotential cycle that is applied at a predetermined frequency in therange of about 1 Hz to about 100000 Hz.
 38. The method of claim 28,further comprising inserting said device into an analyzer configured todetermine whether said measured electrical property associated with saidfirst and said second polymer layers has exceeded a threshold levelassociated with said device usability.
 39. A method of determiningdevice usability, comprising the steps of: providing a device comprisinga first electrical pad; a second electrical pad; and a first polymerlayer contacting at least a portion of said first electrical pad and asecond polymer layer contacting at least a portion of said secondelectrical pad and at least a portion of said first polymer layer;applying a potential across said first and said second electrical pads;measuring an electrical property associated with said first and saidsecond polymer layers; and determining whether the measured electricalproperty associated with said first and said second polymer layers hasexceeded a threshold level associated with said device usability. 40.The method of claim 39, wherein said first polymer layer comprises apolymer matrix and a plasticizer.
 41. The method of claim 40, whereinsaid second polymer layer comprises a polymer matrix, a plasticizer, andan organic salt.
 42. The method of claim 41, wherein said first and saidsecond polymer layers each comprises from 20 to 40 wt. % polymer matrix.43. The method of claim 42, wherein said polymer matrix in each layercomprises a polymer selected from a group consisting of polyvinylchloride, polyurethane, polyvinylacetate, carboxylated PVC, hydroxylatedPVC and polydimethyl siloxane.
 44. The method of claim 43, wherein saidfirst and said second polymer layers each comprises from 60 to 80%plasticizer.
 45. The method of claim 44, wherein said plasticizer ineach layer is selected from a group consisting of trioctyl phosphate(TOP), nitrophenyloctyl ether (NPOE), bisethylhexylsebacate (BEHS),trimethyl trimellitate (TMTT), dioctyl adipate (DOA) and diisobutylphthalate (DIBP).
 46. The method of claim 45, wherein said secondpolymer layer comprises from 0.1 to 10 wt. % of an organic salt.
 47. Themethod of claim 46, wherein said second polymer layer comprises a saltselected from the group consisting of quaternary ammonium tetrakisphenylborate, dodecyl sulfosuccinate, lauryl sulfate, alkyl etherphosphates, benzylkonium, cetylpyrdinium dodecyl sulfosuccinate, laurylsulfate, alkyl ether phosphates, tetramethylammonium, benzylkonium,cetylpyrdinium, an iodide, a bromide, a perchlorate, a zwitterioniccompound, cocamidopropyl hydroxysultaine and quaternary ammonium borate.48. The method of claim 39, wherein said first polymer layer issubstantially circular and has a diameter of from about 20 μm to about 2mm.
 49. The method of claim 39, wherein said second polymer layer issubstantially circular and has a diameter of from about 20 μm to about 2mm.
 50. The method of claim 39, wherein said device further comprises aboundary structure for controlling the spreading of a dispensed firstpolymer layer precursor to a predetermined region of said device. 51.The method of claim 39, wherein said device further comprises a boundarystructure for controlling the spreading of a dispensed second polymerlayer precursor to a predetermined region of the device.
 52. The methodof claim 39, wherein said first and said second pads are separated by adistance of from about 10 μm to about 2 mm.
 53. The method of claim 39,wherein said first and said second polymer layers are domed.
 54. Themethod of claim 39, wherein said electrical property comprises current,resistance, impedance, conductivity, or a combination thereof.
 55. Themethod of claim 54, further comprising measuring an initial currentvalue associated with said first and said second polymer layers whensaid device is manufactured and wherein said threshold level is at leastfive times higher than said initial current value.
 56. The method ofclaim 54, further comprising measuring an initial impedance valueassociated with said first and said second polymer layers when saiddevice is manufactured, wherein said threshold level is at least fivetimes lower than said initial impedance.
 57. The method of claim 39,wherein said potential comprises a sigmoidal potential cycle, a fixedapplied potential, a sequence of fixed applied potential steps, or acombination thereof.
 58. The method of claim 39, wherein said potentialcomprises a potential cycle that is applied at a predetermined frequencyin the range of about 1 Hz to about 100000 Hz.
 59. The method of claim39, further comprising inserting said device into an analyzer configuredto determine whether said measured electrical property associated withsaid first and said second polymer layers has exceeded said thresholdlevel associated with said device usability.
 60. The method of claim 39,where said device further comprises a sensor selected from a groupconsisting of a pH sensor, oxygen sensor, carbon dioxide sensor,hematocrit sensor, glucose sensor, lactate sensor, creatinine sensor,sodium sensor, potassium sensor, chloride sensor, calcium sensor, BNPsensor, troponin sensor, CKMB sensor, NGAL sensor, TSH sensor, D-dimersensor, PSA sensor, PTH sensor, cholesterol sensor, ALT sensor, ASTsensor, prothrombin sensor, APTT sensor, ACT sensor, galectin sensor,and combinations thereof.
 61. A method of claim 39, where said firstpolymer layer is printed onto said device in a first step and saidsecond polymer layer is printed onto said first layer in a second step.62. A method of claim 39, where said electrical response is dependent onan organic salt migrating from said second polymer layer into said firstpolymer layer, wherein said migration is time and temperature dependent.63. A device having a usability threshold, comprising: a firstelectrical pad; a second electrical pad; a first polymer layercontacting at least a portion of said first electrical pad; and a secondpolymer layer contacting at least a portion of said second electricalpad and at least a portion of said first polymer layer, wherein saidfirst and said second polymer layers have an electrical propertyassociated with said device usability threshold.
 64. A devicecomprising: a sensor; a first polymer layer formed on a surface of saiddevice; a second polymer layer formed on said surface of said device; afirst electrical pad; and a second electrical pad, wherein: said surfacecomprises said first and said second electrical pads positioned adjacentto one another and a space therebetween; said first polymer layer coversat least a portion of said first electrical pad and a portion of saidspace therebetween; said second polymer layer contacts at least aportion of said second electrical pad, a portion of said first polymerlayer, and a portion of said space therebetween; a preselected potentialor potential cycle is applied to said first and said second electricalpads and an impedance or current associated with said first and saidsecond polymer layers is measured; and said measured impedance orcurrent is converted to a value indicative of an average shelf life timeremaining for other devices from a same manufacturing lot of saiddevice.
 65. A method of determining device usability, comprising thesteps of: providing a device comprising a first electrical pad; a secondelectrical pad; and a first polymer layer contacting at least a portionof said first electrical pad and a second polymer layer contacting atleast a portion of said second electrical pad and at least a portion ofsaid first polymer layer; applying a potential across said first andsaid second electrical pads; measuring an electrical property associatedwith said first and said second polymer layers; and determining acorrection factor associated with said measured electrical property; andapplying said correction factor to a signal generated by a sensor toproduce a corrected signal.
 66. The method of claim 65, wherein saidcorrection factor is selected from a group consisting of an amperometriccorrection value, a potentiometric correction value, a coulombiccorrection value and a conductivity correction value.
 67. The method ofclaim 65, wherein said sensor is selected from a group consisting of apH sensor, an oxygen sensor, a carbon dioxide sensor, a hematocritsensor, a glucose sensor, a lactate sensor, a creatinine sensor, asodium sensor, a potassium sensor, a chloride sensor, a calcium sensor,a BNP sensor, a troponin sensor, a CKMB sensor, a NGAL sensor, a TSHsensor, a D-dimer sensor, a PSA sensor, a PTH sensor, a cholesterolsensor, an ALT sensor, an AST sensor, a prothrombin sensor, an APTTsensor, an ACT sensor and a galectin sensor.
 68. The method of claim 65,wherein said first polymer layer comprises a polymer matrix and aplasticizer.
 69. The method of claim 65, wherein said second polymerlayer comprises a polymer matrix, a plasticizer, and an organic salt.70. The method of claim 65, wherein said electrical property comprisescurrent, resistance, impedance, conductivity, or a combination thereof.71. The method of claim 70, further comprising measuring an initialcurrent value associated with said first and said second polymer layerswhen said device is manufactured and wherein said threshold level is atleast five times greater than said initial current value.
 72. The methodof claim 70, further comprising measuring an initial impedance valueassociated with said first and said second polymer layers when saiddevice is manufactured, wherein said threshold level is at least fivetimes lower than said initial impedance.
 73. The method of claim 65,wherein said potential comprises a sigmoidal potential cycle, a fixedapplied potential, a sequence of fixed applied potential steps, or acombination thereof.
 74. The method of claim 65, wherein said potentialcomprises a potential cycle that is applied at a predetermined frequencyin the range of about 1 Hz to about 100000 Hz.
 75. The method of claim65, further comprising inserting said device into an analyzer configuredto determine whether said measured electrical property associated withsaid first and said second polymer layers has exceeded a threshold levelassociated with said device usability.